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Faculty


Anait S. Levenson

Professor, Cancer Research and Pharmacology

M.D., Second Moscow State Medical Institute, Moscow, RussiaPh.D., Institute of Tuberculosis, Moscow, RussiaPostdoctoral fellow, University of Virginia, Charlottesville, VA
Research Associate, Northwestern University Medical Center, Chicago, IL

Description

Upon completion of postdoctoral training, Dr. Levenson joined the Northwestern University Medical School faculty where she served for ten continuous years. Dr. Levenson worked at the University of Mississippi Medical Center, Cancer Institute from 2010-15. Dr. Levenson joined Long Island University, College of Pharmacy and Health Sciences as an Associate Dean for Research and Graduate Studies in 2016. Levenson‘s interest is in cancer research, specifically, in molecular mechanisms of hormone-dependent breast and prostate cancer. For the past several years her laboratory has focused on understanding epigenetic mechanisms of prostate cancer progression and metastasis and on utilization of dietary agents, such as resveratrol and its analogs for cancer chemoprevention and treatment. Dr. Levenson is an active reviewer for numerous journals, serves on the Editorial Boards of several journals, and is a member of national and international review panels. She is the author of more than 50 peer-reviewed publications, four book chapters and more than 70 abstracts. Dr. Levenson is a member of American Association for Cancer Research and American Association of Colleges of Pharmacy. As an invited speaker at national and international meetings, Dr. Levenson gave presentations in USA, Greece, Sweden, England, Italy, Denmark, Japan, and Peru. She has been continuously funded throughout her career, and is currently funded by the Department of Defense, Prostate Cancer Research Program, IDEA Development Award.

Publications

  • Chakraborty S, Kumar A, Butt NA, Zhang L, Williams R, Rimando AM, Biswas PK, Levenson AS. Molecular insight into the differential anti-androgenic activity of resveratrol and its natural analogs: In silico approach to understand biological actions. Molecular BioSystems 12, 1702, 2016 http://www.ncbi.nlm.nih.gov/pubmed/27063447
  • Dhar S, Kumar A, Zhang L, Rimando AM, Lage JM, Lewin JR, Atfi A, Zhang X, Levenson AS. Dietary pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer. Oncotarget 7:18469-18484, 2016 http://www.ncbi.nlm.nih.gov/pubmed/26943043
  • Kumar A, Dhar S, Rimando AM, Lage JM, Lewin JR, Zhang X, Levenson AS. Epigenetic potential of resveratrol and analogs in preclinical models of prostate cancer. Annals of New York Academy of Sciences 1348:1-9, 2015 http://www.ncbi.nlm.nih.gov/pubmed26214308
  • Dhar S, Kumar A, Rimando AM, Zhang X, Levenson AS. Resveratrol and pterostilbene epigenetically restore PTEN expression by targeting oncomiRs of the miR-17 family in prostate cancer. Oncotarget 6:27214-27226, 2015 http://www.ncbi.nlm.nih.gov/pubmed/26318586
  • Dhar S, Kumar A, Li K, Zhang X, Tzivion G, Levenson AS. Resveratrol regulates PTEN/Akt pathway through inhibition of MTA1/HDAC unit of the NuRD complex in prostate cancer. Biochimica et Biophysica Acta (Molecular Cell Research) 1853:265-275, 2015 http://www.ncbi.nlm.nih.gov/pubmed/25447541
  • Kumar A, Lin S-Y, Dhar S, Rimando AM, Levenson AS. Stilbenes inhibit androgen receptor expression in 22Rv1 castrate-resistant prostate cancer cells. Journal of Medicinally Active Plants 3: 1-8, 2014
  • Levenson AS*, Kumar A, Zhang X. MTA family of proteins in prostate cancer: biology, significance, and therapeutic opportunities. Cancer Metastasis Reviews 33:929-942, 2014 (*, corresponding author) http://www.ncbi.nlm.nih.gov/pubmed/25332143
  • Chakraborty S, Levenson AS*, and Biswas PK. Structural insights into Resveratrol’s antagonist and partial agonist actions on estrogen receptor alpha. BMC Structural Biology 13:27, 2013 (*, corresponding author) http://www.ncbi.nlm.nih.gov/pubmed/24160181
  • Dias SJ, Zhou X, Ivanovic M, Gailey MP, Dhar S, Zhang L, He Z, Penman AD, Vijayakumar S, Levenson AS. Nuclear MTA1 overexpression is associated with aggressive prostate cancer, recurrence and metastasis in African American men. Scientific Reports 3, 2331: doi:10.1038/srep02331, 2013 http://www.ncbi.nlm.nih.gov/pubmed/23900262
  • Li K, Dias SJ, Rimando AM, Dhar S, Mizuno C, Penman AD, Lewin JR, Levenson AS. Pterostilbene acts through metastasis-associated protein 1 to inhibit tumor progression and metastasis in prostate cancer. PLoS ONE 8: e57542, 2013 http://www.ncbi.nlm.nih.gov/pubmed/23469203
  • Dias SJ, Li K, Rimando AM, Dhar S, Mizuno C, Penman AD, Levenson AS. Trimethoxy-resveratrol and piceatannol administered orally suppress and inhibit tumor formation and growth in prostate cancer xenografts. The Prostate 73: 1135-1146, 2013 http://www.ncbi.nlm.nih.gov/pubmed/23657951
  • Kai L and Levenson AS. Combination of resveratrol and antiandrogen flutamide has synergistic effect on androgen receptor inhibition in prostate cancer cells. Anticancer Research 33: 3323-3330, 2011 http://www.ncbi.nlm.nih.gov/pubmed/21965742
  • Dhar S, Hicks C and Levenson AS. Resveratrol and prostate cancer: promising role for microRNAs. Molecular Nutrition and Food Research 55: 1219-1229, 2011 http://www.ncbi.nlm.nih.gov/pubmed/21714127
  • Kai L, Wang J, Ivanovic M, Chung Y-T, Laskin WB, Schulze-Hoepfner F, Mirochnik Y, Satcher RL and Levenson AS. Targeting prostate cancer angiogenesis through metastasis-associated protein 1 (MTA1). The Prostate 71: 268-280, 2011http://www.ncbi.nlm.nih.gov/pubmed/20717904
  • Kai L, Samuel SK and Levenson AS. Resveratrol enhances p53 acetylation and apoptosis in prostate cancer by inhibiting MTA1/NuRD complex. International Journal of Cancer 126:1538-48, 2010 (Cover story and art, April 1) http://www.ncbi.nlm.nih.gov/pubmed/19810103
  • Mazan-Mamczarz K, Hagner PR, Corl S, Srikantan S, Wood WH, Becker KG, Gorospe M, Keene JD, Levenson AS, Gartenhaus R. Post-transcriptional gene regulation by HuR promotes a more tumorigenic phenotype. Oncogene 27:6151-63, 2008 http://www.ncbi.nlm.nih.gov/pubmed/18641687
  • Wang J, Jarrett J, Huang C-C, Satcher RL, Levenson AS. Identification of estrogen-regulated metastasis-associated genes involved in breast cancer bone metastases to the bone. Clinical & Experimental Metastasis 24:411-22, 2007 http://www.ncbi.nlm.nih.gov/pubmed/17593529
  • Wang J, Levenson AS*, Satcher RL. Identification of a unique set of genes altered during cell-cell contact in an in vitro model of prostate cancer bone metastasis. International Journal of Molecular Medicine 17: 849-56, 2006 (*, corresponding author) http://www.ncbi.nlm.nih.gov/pubmed/16596270
  • Levenson AS*, Thurn TE, Simons LA, Veliceasa D, Jarrett J, Osipo C, Jordan VC, Volpert OV, Satcher RL, Gartenhaus RB. Overexpression of MCT1 oncogene contributes to increase in vivo tumorigenicity of MCF7 cells by promotion of angiogenesis and inhibition of apoptosis. Cancer Research 65: 10651-6, 2005 (*, corresponding author) http://www.ncbi.nlm.nih.gov/pubmed/16322206
  • Melnikov AA, Gartenhaus RB, Levenson AS, Motchoulskaia NA, Levenson VV. MSRE-PCR for analysis of gene-specific DNA methylation. Nucleic Acids Research 33: e93, 2005 http://www.ncbi.nlm.nih.gov/pubmed/15944447
  • Satcher RL, Dvorkin K, Levenson AS, Vandenbroek T and Stupp S.I. Gene expression in cancer cells is influenced by contact with bone cells in a novel co-culture system that models bone metastasis. Clinical Orthopaedics and Related Research 426: 54-63, 2004 http://www.ncbi.nlm.nih.gov/pubmed/15346052
  • Davidovich IA, Levenson AS, Levenson VV. Overexpression of DcR1 and survivin in genetically modified cells with pleiotropic drug resistance. Cancer Letters 211: 189-197, 2004 http://www.ncbi.nlm.nih.gov/pubmed/15219942
  • Gehm BD, Levenson AS, Liu H, Lee E-J, Amundsen BM, Cushman M, Jordan VC and Jameson JL. Estrogenic effects of resveratrol in breast cancer cells expressing mutant and wild- type estrogen receptors: role of AF1 and AF2. Journal of Steroid Biochemistry and Molecular Biology 88: 223-234, 2004 http://www.ncbi.nlm.nih.gov/pubmed/15120416
  • Levenson AS, Gehm BD, Timm Pearce S, Horiguchi J, Simons LA, Ward III JE, Jameson JL and Jordan VC. Resveratrol acts as an estrogen receptor (ER) agonist in breast cancer cells stably transfected with ERα. International Journal of Cancer 104: 587-596, 2003 (Cover story and art, May 1, *, corresponding author) http://www.ncbi.nlm.nih.gov/pubmed/12594813
  • Levenson AS*, Kliakhandler IL, Pease KM, Svoboda KM, Kaiser SA, Ward III JE and Jordan VC. Molecular classification of SERMs on the basis of gene expression profiles of breast cancer cells expressing ER alpha. British Journal of Cancer 87: 449-456, 2002 (*, corresponding author) http://www.ncbi.nlm.nih.gov/pubmed/12177783
  • Levenson AS*, Svoboda KM, Pease KM, Kaiser SA, Chen B, Simons LA, Jovanovic BD, Dyck PA and Jordan VC. Gene expression profiles with activation of the ER-SERM complex in breast cancer cells expressing wt ER. Cancer Research 62: 4419-4426, 2002 (*, corresponding author) http://www.ncbi.nlm.nih.gov/pubmed/12154049
  • Jordan VC, MacGregor Schafer JI, Levenson AS, Liu H, Pease KM, Simons LA and Zapf JW. Molecular classification of estrogens. Cancer Research 61: 6619-6623, 2001 http://www.ncbi.nlm.nih.gov/pubmed/11559523
  • MacGregor Schafer JI, Liu H, Levenson AS, Horiguchi J, Chen Z and Jordan VC. Estrogen receptor alpha mediated induction of the transforming growth factor alpha gene by estradiol and 4-hydroxytamoxifen in MDA-MB-231 breast cancer cells. Journal of Steroid Biochemistry and Molecular Biology 78: 41-50, 2001 http://www.ncbi.nlm.nih.gov/pubmed/11530283
  • Levenson AS, MacGregor Schafer JI, Bentrem DJ, Pease KM and Jordan VC. Control of the estrogen-like actions of the tamoxifen-estrogen receptor complex by the surface amino acid at position 351. Journal of Steroid Biochemistry and Molecular Biology 76: 61-70, 2001 http://www.ncbi.nlm.nih.gov/pubmed/11384864
  • Levenson AS and Jordan VC. Selective Estrogen Receptor Modulation. Millennium Review 2000. European Journal of Cancer 35: 1628-1639, 1999 http://www.ncbi.nlm.nih.gov/pubmed/10711240
  • Chen S-J, Yuan W, Mori Y, Levenson AS, Troyanowska M and Varga J. Stimulation of type I collagen transcription in human skin fibroblasts by TGF-β: involvement of Smad 3. Journal Investigative Dermatology 112: 49-57, 1999 http://www.ncbi.nlm.nih.gov/pubmed/9886263
  • Levenson AS, Kwaan HC, Svoboda KM, Weiss IM, Sakurai S and Jordan VC. Estradiol regulation of components of the plasminogen-plasmin system in MDA-MB-231 human breast cancer cells stably expressing the estrogen receptor. British Journal of Cancer 78: 88-95, 1998 http://www.ncbi.nlm.nih.gov/pubmed/9662256
  • Levenson AS, Tonetti DA and Jordan VC. The estrogen-like effect of 4-hydroxytamoxifen (4-OHT) on induction of transforming growth factor alpha (TGF-α) mRNA in MDA-MB-231 breast cancer cells stably expressing the estrogen receptor (ER). British Journal of Cancer 77: 1812-1819, 1998 http://www.ncbi.nlm.nih.gov/pubmed/9667651
  • Levenson AS and Jordan VC. The key to the antiestrogenic mechanism of raloxifene is amino acid 351 (Asp) in the estrogen receptor. Cancer Research 58: 1872-1875, 1998 http://www.ncbi.nlm.nih.gov/pubmed/9581827
  • Levenson AS, Wolf DM, Catherino WH, Takei H and Jordan VC. Understanding the antiestrogenic actions of raloxifene and a mechanism of drug resistance to tamoxifen. Breast Cancer 5: 99-106, 1998 http://www.ncbi.nlm.nih.gov/pubmed/11091634
  • Levenson AS, Svoboda KM, Kwaan HC and Jordan VC. Agonist activity of antiestrogen-receptor complexes to regulate urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) endogenous gene expression in breast cancer cells. Cancer Letters 125: 215-220, 1998 http://www.ncbi.nlm.nih.gov/pubmed/9566718
  • Levenson AS and Jordan VC. MCF-7: The first hormone responsive breast cancer cell line. Perspectives in Cancer Research. Cancer Research 57: 3071-3078, 1997 http://www.ncbi.nlm.nih.gov/pubmed/9242427
  • Levenson AS, Catherino WH, and Jordan VC. Estrogenic activity is increased for an antiestrogen by a natural mutation of the estrogen receptor. Journal of Steroid Biochemistry and Molecular Biology 60: 261-268, 1997 http://www.ncbi.nlm.nih.gov/pubmed/9219916
  • Shugart EC, Constance CM, Levenson AS and Umek RM. Differential expression of gas and gadd genes at distinct growth arrest points during adipocyte development. Cell Growth and Differentiation 6: 1541-1547, 1995 http://www.ncbi.nlm.nih.gov/pubmed/9019159
  • Levenson AS and Jordan VC. Transfection of human estrogen receptor (ER) cDNA into ER-negative mammalian cell lines. Journal of Steroid Biochemistry and Molecular Biology 51: 229-239, 1994 http://www.ncbi.nlm.nih.gov/pubmed/7826884

Research Synopsis

Identification of "bone metastatic signature" couple of years ago allowed us to focus on selected candidate genes that hold promise as potential biomarkers and therapeutic targets of bone metastases. We have shown that one of these genes, metastasis-associated protein 1 (MTA1), which is a chromatin modifier, plays a critical role in prostate cancer progression and metastasis by inhibiting apoptosis and promoting angiogenesis. We also have evidence that MTA1 can serve as an independent prognostic marker for aggressive prostate cancer, particularly in African American men. Currently, we aim to understand MTA1-mediated genetic and epigenetic mechanisms in prostate cancer pathogenesis. We have shown that MTA1/ HDAC1/2 inactivate tumor suppressors p53 and PTEN leading to inhibition of apoptosis and promotion of pAkt-mediated survival pathways. Using small interfering RNA technology, we have found that the loss of MTA1 decreases the proliferative and metastatic potential of cells in vitro and in vivo, particularly through mechanisms associated with the induction of apoptosis and reduction of angiogenesis. In addition, the role of MTA1 in the epithelial-to-mesenchymal transition and radioresistance in prostate cancer is of interest. While working with already identified target candidates such as pAkt, HIF1-α, and E-cadherin, we are interested in identifying new potential MTA1-associated high-risk biomarkers. At the moment, we are analyzing our MTA1 ChIP-Seq data which identified about 33,000 direct MTA1-DNA binding peaks in the mouse genome. Another active project is on epigenetic regulatory network that is represented by microRNAs and Epi-microRNAs. Finally, one of the major interest of the lab is potential chemopreventive and therapeutic efficacy of dietary stilbenes and other phytochemicals in cancer. We found that pterostilbene, a natural analog of resveratrol, inhibits MTA1 and rescues acetylation of tumor suppressors’ p53 and PTEN in prostate cancer. The novel MTA1-mediated epigenetic mechanisms of action of dietary compounds is under intensive investigation with pre-clinical animal testing using xenografts and transgenic mice.